Explore studies of anxiety mood.
ICV alpha-endorphin (2.5-10 nmol), beta-endorphin (0.38-1.5 nmol), and gamma-endorphin (2.5-10 nmol) did not affect conditioned suppression or forced swim immobility in mice.
Katoh, A; Nabeshima, T; Ukai, R; Kameyama, T · Animal Study
Three CRF receptor subtypes (CRF1, CRF2alpha, CRF2beta) and a CRF-binding protein coordinate stress responses, and newly developed non-peptide CRF antagonists show therapeutic promise.
Behan, D P; Grigoriadis, D E; Lovenberg, T; Chalmers, D; Heinrichs, S; Liaw, C; De Souza, E B · Review
NPY mediates analgesia and hyperalgesia through distinct receptor subtypes, alongside established roles in blood pressure regulation and anxiety modulation.
Munglani, R; Hudspith, M J; Hunt, S P · Review
Low blood pressure responders to mental stress had significantly higher beta-endorphin release than high responders, suggesting endogenous opioids buffer the cardiovascular stress response.
Fontana, F; Bernardi, P; Pich, E M; Boschi, S; De Iasio, R; Spampinato, S; Grossi, G · Clinical Trial
Asymptomatic dilated cardiomyopathy patients had normal resting opioid peptide levels but showed altered opioid peptide responses to mental stress, alongside elevated ANF levels.
Fontana, F; Bernardi, P; Merlo Pich, E; Tartuferi, L; Boschi, S; De Iasio, R; Spampinato, S · Clinical Trial
BPC-157 co-administration with chronic diazepam (10 days) prevented tolerance development, maintained anticonvulsant efficacy, and reduced withdrawal seizure severity at both 10 μg/kg and 10 ng/kg doses in rats.
Jelovac, N; Sikiric, P; Rucman, R; Petek, M; Perovic, D; Marovic, A; Anic, T; Seiwerth, S; Mise, S; Pigac, B; Duplancie, B; Turkovic, B; Dodig, G; Prkacin, I; Stancic-Rokotov, D; Zoricic, I; Aralica, G; Sebecic, B; Ziger, T; Slobodnjak, Z · Animal Study
Non-peptide CRF1 receptor antagonists selectively block stress signaling and show anxiolytic and antidepressant effects in animal models, with potential clinical applications spanning anxiety, depression, addiction, and inflammation.
McCarthy, J R; Heinrichs, S C; Grigoriadis, D E · Review
Intranasal NPY promoted sleep and reduced ACTH and cortisol in healthy young men, demonstrating CRH-opposing anxiolytic and sedative effects with potential therapeutic applications for depression and insomnia.
Antonijevic, I A; Murck, H; Bohlhalter, S; Frieboes, R M; Holsboer, F; Steiger, A · RCT
Special forces soldiers showed higher plasma NPY during extreme stress and faster post-stress recovery compared to regular troops, with higher NPY correlating with better performance and less psychological distress.
Morgan, C A; Wang, S; Southwick, S M; Rasmusson, A; Hazlett, G; Hauger, R L; Charney, D S · Cohort
BPC-157 showed antidepressant activity in both the Porsolt forced swim test (reduced immobility) and chronic unpredictable stress model in rats, with effects comparable to established antidepressants.
Sikiric, P; Separovic, J; Buljat, G; Anic, T; Stancic-Rokotov, D; Mikus, D; Marovic, A; Prkacin, I; Duplancic, B; Zoricic, I; Aralica, G; Lovric-Bencic, M; Ziger, T; Perovic, D; Rotkvic, I; Mise, S; Hanzevacki, M; Hahn, V; Seiwerth, S; Turkovic, B; Grabarevic, Z; Petek, M; Rucman, R · Animal Study
ICV and intrathecal anti-dynorphin antibodies blocked immobilization stress-induced analgesia, while anti-enkephalin and anti-endorphin antibodies did not, establishing dynorphin as the specific mediator at both brain and spinal levels.
Suh, H W; Song, D K; Huh, S O; Kim, Y H · Animal Study
BPC-157 at 10 μg/kg and 10 ng/kg IP produced anxiolytic effects comparable to diazepam in both the shock probe/burying test (reduced defensive burying) and light/dark test (increased light exploration) in rats.
Sikiric, P; Jelovac, N; Jelovac-Gjeldum, A; Dodig, G; Staresinic, M; Anic, T; Zoricic, I; Ferovic, D; Aralica, G; Buljat, G; Prkacin, I; Lovric-Bencic, M; Separovic, J; Seiwerth, S; Rucman, R; Petek, M; Turkovic, B; Ziger, T · Animal Study
Anxiety patients showed accelerated enkephalin degradation, and Selank's anxiolytic effect correlated with inhibition of enkephalin-degrading enzymes, preserving endogenous opioid-mediated anxiety relief.
Zozulya, A A; Kost, N V; Yu Sokolov, O; Gabaeva, M V; Grivennikov, I A; Andreeva, L N; Zolotarev, Y A; Ivanov, S V; Andryushchenko, A V; Myasoedov, N F; Smulevich, A B · Clinical Trial
Expanded CRF peptide family including urocortins reveals distinct CRF1 (anxiety/depression) and CRF2 (stress coping/appetite/cardiovascular) receptor functions, enabling receptor-specific drug development.
Dautzenberg, Frank M; Hauger, Richard L · Review
Opioid gene knockouts reveal distinct, non-redundant roles: enkephalins in analgesia and reward, beta-endorphin in stress analgesia and respiratory control, dynorphins in pain and emotional regulation — each family has a specific functional niche.
Kieffer, Brigitte L; Gavériaux-Ruff, Claire · Review
CRF1 promotes anxiety and depression while CRF2 may have opposing anxiolytic/stress-recovery effects, with urocortins as natural CRF2-preferring ligands enabling receptor-specific therapeutic targeting.
Reul, Johannes M H M; Holsboer, Florian · Review
BPC-157 attenuated chronic amphetamine-induced tolerance, behavioral sensitization, and withdrawal disturbances in rats, demonstrating comprehensive dopamine system stabilization against stimulant drug-induced neuroplasticity.
Sikiric, Predrag; Jelovac, Nikola; Jelovac-Gjeldum, Andjelka; Dodig, Goran; Staresinic, Mario; Anic, Tomislav; Zoricic, Ivan; Rak, Davor; Perovic, Darko; Aralica, Gorana; Buljat, Gojko; Prkacin, Ingrid; Lovric-Bencic, Martina; Separovic, Jadranka; Seiwerth, Sven; Rucman, Rudolf; Petek, Marijan; Turkovic, Branko; Ziger, Tihomil; Boban-Blagaic, Alenka; Bedekovic, Vlado; Tonkic, Ante; Babic, Slaven · Animal Study
Selank reduced anxiety behavior in naturally anxious BALB/c mice while modifying enkephalin-degrading enzyme activity, with the anxiolytic effect phenotype-dependent — working most in animals with the greatest enkephalin degradation.
Sokolov, O Yu; Meshavkin, V K; Kost, N V; Zozulya, A A · Animal Study
Multiple neuropeptide systems (CRF, NPY, substance P/NK1, galanin, vasopressin, nociceptin) offer novel antidepressant and anxiolytic targets with mechanisms fundamentally different from monoamine-based drugs.
Holmes, Andrew; Heilig, Markus; Rupniak, Nadia M J; Steckler, Thomas; Griebel, Guy · Review
Selank and tuftsin-family peptides improved adaptive behavior in stressed animals in a phenotype-dependent manner, with different peptides optimal for different emotional reactivity types — supporting personalized peptide anxiolytic therapy.
Kozlovskaya, M M; Kozlovskii, I I; Val'dman, E A; Seredenin, S B · Animal Study
Both short and long maternal separation produced distinct, persistent alterations in brain opioid peptide levels (dynorphin, met-enkephalin) across reward and stress regions in adult rats, demonstrating lasting neurochemical consequences of early life experience.
Ploj, Karolina; Roman, Erika; Nylander, Ingrid · Animal Study
CP-154,526 showed anxiolytic effects across multiple animal models, antidepressant activity, and HPA axis modulation without sedation, providing the most comprehensive validation of CRF1 antagonism as a psychiatric drug mechanism.
Seymour, Patricia A; Schmidt, Anne W; Schulz, David W · Review
Depression, panic, and PTSD show distinct stress neurohormone patterns (CRF, vasopressin, NPY alterations), with ANP demonstrating anxiolytic properties — disorder-specific peptide profiles enabling targeted therapy.
Ströhle, A; Holsboer, F · Review
All three endogenous opioid peptide families (endorphins, enkephalins, dynorphins) inversely correlated with aggression across brain regions, with each acting through distinct receptor systems (mu, delta, kappa) and neural circuits.
Tordjman, Sylvie; Carlier, Michèle; Cohen, David; Cesselin, François; Bourgoin, Sylvie; Colas-Linhart, Nicole; Petiet, Anne; Perez-Diaz, Fernando; Hamon, Michel; Roubertoux, Pierre L · Animal Study
Met- and leu-enkephalin immunoreactive neurons were distributed throughout social behavior brain nuclei (BNST, medial amygdala, MPOA, lateral septum, PAG) in male hamsters, providing an anatomical framework for opioid peptide regulation of social and reproductive behaviors.
Holt, Avril Genene; Newman, Sarah Winans · Animal Study
Maternal separation significantly altered maternal care patterns but produced only subtle changes in adult offspring brain opioid peptides and behavior, suggesting compensatory mechanisms partially buffer against early-life adversity effects.
Marmendal, Maarit; Roman, Erika; Eriksson, C J Peter; Nylander, Ingrid; Fahlke, Claudia · Animal Study
SAR studies on astressin identified the minimal CRF antagonist sequence retaining biological activity at both CRF1 and CRF2 receptors, advancing design of smaller, more drug-like peptide antagonists for stress-related psychiatric disorders.
Rijkers, Dirk T S; Kruijtzer, John A W; van Oostenbrugge, Marja; Ronken, Eric; den Hartog, Jack A J; Liskamp, Rob M J · In Vitro
Amygdalar NPY-CRF interactions constitute an anxiety-resilience balance: CRF promotes fear/anxiety through CRF1 while NPY opposes through Y1 receptors — imbalance drives anxiety disorders, PTSD, and addiction.
Sajdyk, Tammy J; Shekhar, Anantha; Gehlert, Donald R · Review
BPC-157 produced region-specific changes in brain serotonin synthesis measured by alpha-methyl-L-tryptophan autoradiography — increasing synthesis in some regions while decreasing it in others, providing the serotonergic basis for its mood-modulating properties.
Tohyama, Y; Sikirić, P; Diksic, M · Animal Study
BPC-157 effectively counteracted serotonin syndrome signs (hyperthermia, tremor, rigidity, agitation) induced by multiple serotonergic drugs in rats, demonstrating serotonergic system modulation complementing its known dopaminergic and GABAergic interactions.
Boban Blagaic, Alenka; Blagaic, Vladimir; Mirt, Mirela; Jelovac, Nikola; Dodig, Goran; Rucman, Rudolf; Petek, Marijan; Turkovic, Branko; Anic, Tomislav; Dubovecak, Miroslav; Staresinic, Mario; Seiwerth, Sven; Sikiric, Predrag · Animal Study
CRF/urocortin system activation drives the stress/withdrawal component of cannabis, nicotine, and alcohol dependence through CRF1-mediated anxiety during abstinence, creating a negative reinforcement cycle that maintains substance use.
Bruijnzeel, Adrie W; Gold, Mark S · Review
CRF family peptides (CRF, urocortin 1-3) modulate peripheral inflammation through CRF1 (generally pro-inflammatory) and CRF2 (generally anti-inflammatory) receptors on immune cells, gut, and skin — with therapeutic applications for IBD, arthritis, and dermatitis.
Gravanis, Achille; Margioris, Andrew N · Review
Intranasal oxytocin attenuated amygdala reactivity to threatening facial expressions measured by fMRI in healthy humans, providing the first neural imaging evidence for oxytocin's anxiolytic mechanism through direct fear-circuit modulation.
Kirsch, Peter; Esslinger, Christine; Chen, Qiang; Mier, Daniela; Lis, Stefanie; Siddhanti, Sarina; Gruppe, Harald; Mattay, Venkata S; Gallhofer, Bernd; Meyer-Lindenberg, Andreas · RCT
Bulimia nervosa patients demonstrated blunted post-meal ghrelin suppression and altered PYY3-36 response compared to healthy controls, indicating disrupted gut peptide satiety signaling that may perpetuate the binge-purge cycle.
Kojima, Shinya; Nakahara, Toshihiro; Nagai, Nobuatsu; Muranaga, Tetsuro; Tanaka, Muneki; Yasuhara, Daisuke; Masuda, Akinori; Date, Yukari; Ueno, Hiroaki; Nakazato, Masamitsu; Naruo, Tetsuro · Clinical Trial
DMP696 and DMP904 demonstrated CRF1 receptor antagonist anxiolytic activity with distinct pharmacokinetic, selectivity, and efficacy profiles across anxiety models — advancing multiple CRF1 drug candidates with different clinical potential.
Li, Yu-Wen; Fitzgerald, Lawrence; Wong, Harvey; Lelas, Snjezana; Zhang, Ge; Lindner, Mark D; Wallace, Tanya; McElroy, John; Lodge, Nicholas J; Gilligan, Paul; Zaczek, Robert · Review
Adolescent nicotine exposure produced lasting increases in CRF-like and NPY-like immunoreactivity in amygdala and hypothalamic stress regions in adult rats, correlating with increased anxiety — adolescent nicotine permanently alters brain stress peptide systems.
Slawecki, Craig J; Thorsell, Annika K; El Khoury, Aram; Mathé, Aleksander A; Ehlers, Cindy L · Animal Study
The novel selective CRF1 agonist cortagine enabled clear dissection of CRF receptor roles: CRF1 activation drives anxiety/depression-like behavior while CRF2 activation promotes stress coping — precise tools for receptor-specific psychiatric drug development.
Todorovic, Cedomir; Jahn, Olaf; Tezval, Hossein; Hippel, Cathrin; Spiess, Joachim · Review
Children with anorexia nervosa demonstrated disrupted entero-insular axis responses: abnormal GLP-1, insulin, glucose, and gut peptide dynamics after meals compared to healthy controls — gut hormone dysfunction may perpetuate the disease beyond psychological factors.
Tomasik, Przemyslaw J; Sztefko, Krystyna; Starzyk, Jerzy; Rogatko, Iwona; Szafran, Zdzisław · Clinical Trial
GH secretagogues modulate HPA axis regulation through interactions with GABAergic, mineralocorticoid, and somatotropic pathways — explaining cortisol co-release during GH stimulation and the stress-axis implications of chronic GH secretagogue use.
Giordano, Roberta; Pellegrino, Micaela; Picu, Andreea; Bonelli, Lorenza; Balbo, Marcella; Berardelli, Rita; Lanfranco, Fabio; Ghigo, Ezio; Arvat, Emanuela · Review
Naloxone blocked Selank's depriming effect on apomorphine-induced dopaminergic behavioral manifestations, directly confirming opioid system involvement in Selank's anxiolytic mechanism — linking its anti-anxiety action to enkephalin protection.
Meshavkin, V K; Kost, N V; Sokolov, O Yu; Zolotarev, Yu A; Myasoedov, N F; Zozulya, A A · Animal Study
GHS-R gene polymorphism (Leu72Met) was significantly associated with bulimia nervosa in Japanese women, providing genetic evidence linking ghrelin receptor variation to eating disorder susceptibility.
Miyasaka, K; Hosoya, H; Sekime, A; Ohta, M; Amono, H; Matsushita, S; Suzuki, K; Higuchi, S; Funakoshi, A · Cross Sectional
Endogenous opioid peptides regulate HPA axis stress reactivity through hypothalamic CRF and ACTH modulation, with opioid system disruption producing altered cortisol responses — explaining stress hormone dysregulation in chronic pain, addiction, and stress disorders.
Bilkei-Gorzo, Andras; Racz, Ildiko; Michel, Kerstin; Mauer, Daniela; Zimmer, Anne; Klingmüller, Dietrich; Zimmer, Andreas · Animal Study
Obese women with BED showed distinct postprandial gut peptide profiles (altered ghrelin, PYY3-36, GLP-1) compared to non-binge obese controls, identifying BED-specific gut hormone dysfunction beyond general obesity-related appetite changes.
Geliebter, Allan; Hashim, Sami A; Gluck, Marci E · Clinical Trial
Postnatal environment quality produced lasting changes in brain opioid peptide levels (dynorphin, enkephalin) across development into adulthood in Wistar rats, demonstrating enduring early-life programming of the opioid system that may predispose to later psychopathology.
Gustafsson, Lisa; Oreland, Sadia; Hoffmann, Pernilla; Nylander, Ingrid · Animal Study
AVPR1a and OXTR genetic polymorphisms are associated with human social behavior variation: autism spectrum features, pair-bonding patterns, empathy levels, and social anxiety — establishing the genetic basis for neuropeptide-mediated social behavior.
Israel, Salomon; Lerer, Elad; Shalev, Idan; Uzefovsky, Florina; Reibold, Mathias; Bachner-Melman, Rachel; Granot, Roni; Bornstein, Gary; Knafo, Ariel; Yirmiya, Nurit; Ebstein, Richard P · Review
Chronic psychosocial stress produced CRF alterations in the PVN and central amygdala correlating with increased anxiety-like behavior, mapping how chronic social stress reprograms the brain's CRF stress system to produce persistent anxiety.
Kozicz, T; Bordewin, L A P; Czéh, B; Fuchs, E; Roubos, E W · Animal Study
Intranasal oxytocin and vasopressin modulate human social brain circuits (amygdala fear, insula empathy, prefrontal evaluation) as demonstrated by fMRI — neuropeptide modulation of social cognition with therapeutic implications for autism and social anxiety.
Meyer-Lindenberg, Andreas · Review
CRF-CRFR1 molecular recognition involves a two-step binding model: C-terminal CRF helix binds the receptor N-terminus (affinity), then N-terminal CRF contacts the receptor core (activation) — structural basis for designing CRF receptor-selective drugs.
Pioszak, Augen A; Parker, Naomi R; Suino-Powell, Kelly; Xu, H Eric · In Vitro
Two different autism spectrum disorder (ASD) mouse models were used. One was created by prenatal valproic acid exposure (environmental cause), the other by the Nl3R451C genetic mutation (genetic cause). Both had impaired social memory, the ability to distinguish familiar from novel mice. Selectively expressing hM3Dq (an activating DREADD receptor) in oxytocin receptor-positive (OXTR+) neurons in the lateral septum (LS) allowed researchers to activate these specific neurons with a chemical trigger. In the valproic acid model, activation restored social memory in the three-chamber social test. In the Nl3R451C model, social memory was restored in a single-field test. Both represent core ASD symptoms. The OXTR+ neurons in the LS project to the CA1 region of the hippocampus, suggesting social memory depends on an oxytocin-responsive circuit from the lateral septum to the hippocampus. This identifies a specific neural pathway that could explain how intranasal oxytocin therapy improves social symptoms in ASD patients.
Horiai, Machi; Otsuka, Ayano; Hidema, Shizu; Hiraoka, Yuichi; Hayashi, Ryotaro; Miyazaki, Shinji; Furuse, Tamio; Mizukami, Hiroaki; Teruyama, Ryoichi; Tamura, Masaru; Bito, Haruhiko; Maejima, Yuko; Shimomura, Kenju; Nishimori, Katsuhiko · Animal Study (Mice, Neuroscience)
Single-dose intranasal NPY (6.8 mg) reduced MADRS by 10.3 points at 24h vs 5.6 for placebo (P=0.04, d=0.67) in MDD patients; effect not significant at 48h.
Mathé, Aleksander A; Michaneck, Miranda; Berg, Elisabeth; Charney, Dennis S; Murrough, James W · Rct